A comprehensive molecular analysis of 113 primary ovarian clear
cell carcinomas reveals common therapeutically significant
aberrations

J 2023

A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations

STRUZINSKA, Ivana, Nikola HAJKOVA, Jan HOJNY, Eva KRKAVCOVA, Romana MICHALKOVA et. al.

Basic information

Original name

A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations

Authors

STRUZINSKA, Ivana (203 Czech Republic, guarantor), Nikola HAJKOVA (203 Czech Republic), Jan HOJNY (203 Czech Republic), Eva KRKAVCOVA (203 Czech Republic), Romana MICHALKOVA (203 Czech Republic), Jiri DVORAK (203 Czech Republic), Kristyna NEMEJCOVA (203 Czech Republic), Radoslav MATEJ (203 Czech Republic), Jan LACO (203 Czech Republic), Jana DROZENOVA (203 Czech Republic), Pavel FABIAN (203 Czech Republic), Jitka HAUSNEROVÁ (203 Czech Republic, belonging to the institution), Gabor MEHES (203 Czech Republic), Petr SKAPA (203 Czech Republic), Marian SVAJDLER (203 Czech Republic), David CIBULA (203 Czech Republic), Filip FRUHAUF (203 Czech Republic), Michaela Kendall KENDALL BARTU (203 Czech Republic) and Pavel DUNDR (203 Czech Republic)

Edition

Diagnostic Pathology, LONDON, BMC, 2023, 1746-1596

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30109 Pathology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.600 in 2022

RIV identification code

RIV/00216224:14110/23:00131201

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1186/s13000-023-01358-0

UT WoS

001002555100001

Keywords in English

Capture DNA NGS; RNA-Seq; Rare ovarian tumors; POLE mutation

Abstract

V originále

BackgroundMolecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking.Methods113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance.ResultsThe most frequent mutations were detected in genes ARID1A, PIK3CA, TERTp, KRAS, TP53, ATM, PPP2R1A, NF1, PTEN, and POLE (51,47,27,18,13,10,7,6,6, and 4%, respectively). TMB-High cases were detected in 9% of cases. Cases with POLEmut and/or MSI-High had better relapse-free survival. RNA-Seq revealed gene fusions in 14/105 (13%) cases, and heterogeneous expression pattern. The majority of gene fusions affected tyrosine kinase receptors (6/14; four of those were MET fusions) or DNA repair genes (2/14). Based on the mRNA expression pattern, a cluster of 12 OCCCs characterized by overexpression of tyrosine kinase receptors (TKRs) AKT3, CTNNB1, DDR2, JAK2, KIT, or PDGFRA (p < 0.00001) was identified.ConclusionsThe current work has elucidated the complex genomic and transcriptomic molecular hallmarks of primary OCCCs. Our results confirmed the favorable outcomes of POLEmut and MSI-High OCCC. Moreover, the molecular landscape of OCCC revealed several potential therapeutical targets. Molecular testing can provide the potential for targeted therapy in patients with recurrent or metastatic tumors.

Links

90233, large research infrastructures

Name: BBMRI.cz IV

Citovat

STRUZINSKA, Ivana, Nikola HAJKOVA, Jan HOJNY, Eva KRKAVCOVA, Romana MICHALKOVA, Jiri DVORAK, Kristyna NEMEJCOVA, Radoslav MATEJ, Jan LACO, Jana DROZENOVA, Pavel FABIAN, Jitka HAUSNEROVÁ, Gabor MEHES, Petr SKAPA, Marian SVAJDLER, David CIBULA, Filip FRUHAUF, Michaela Kendall KENDALL BARTU and Pavel DUNDR. A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations. Diagnostic Pathology. LONDON: BMC, 2023, vol. 18, No 1, p. 1-12. ISSN 1746-1596. Available from: https://dx.doi.org/10.1186/s13000-023-01358-0.

@article{2296992,
   author = {Struzinska, Ivana and Hajkova, Nikola and Hojny, Jan and Krkavcova, Eva and Michalkova, Romana and Dvorak, Jiri and Nemejcova, Kristyna and Matej, Radoslav and Laco, Jan and Drozenova, Jana and Fabian, Pavel and Hausnerová, Jitka and Mehes, Gabor and Skapa, Petr and Svajdler, Marian and Cibula, David and Fruhauf, Filip and Kendall Bartu, Michaela Kendall and Dundr, Pavel},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13000-023-01358-0},
   keywords = {Capture DNA NGS; RNA-Seq; Rare ovarian tumors; POLE mutation},
   language = {eng},
   issn = {1746-1596},
   journal = {Diagnostic Pathology},
   title = {A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations},
   url = {https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-023-01358-0},
   volume = {18},
   year = {2023}
}

TY  - JOUR
ID  - 2296992
AU  - Struzinska, Ivana - Hajkova, Nikola - Hojny, Jan - Krkavcova, Eva - Michalkova, Romana - Dvorak, Jiri - Nemejcova, Kristyna - Matej, Radoslav - Laco, Jan - Drozenova, Jana - Fabian, Pavel - Hausnerová, Jitka - Mehes, Gabor - Skapa, Petr - Svajdler, Marian - Cibula, David - Fruhauf, Filip - Kendall Bartu, Michaela Kendall - Dundr, Pavel
PY  - 2023
TI  - A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations
JF  - Diagnostic Pathology
VL  - 18
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - BMC
SN  - 17461596
KW  - Capture DNA NGS
KW  - RNA-Seq
KW  - Rare ovarian tumors
KW  - POLE mutation
UR  - https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-023-01358-0
N2  - BackgroundMolecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking.Methods113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance.ResultsThe most frequent mutations were detected in genes ARID1A, PIK3CA, TERTp, KRAS, TP53, ATM, PPP2R1A, NF1, PTEN, and POLE (51,47,27,18,13,10,7,6,6, and 4%, respectively). TMB-High cases were detected in 9% of cases. Cases with POLEmut and/or MSI-High had better relapse-free survival. RNA-Seq revealed gene fusions in 14/105 (13%) cases, and heterogeneous expression pattern. The majority of gene fusions affected tyrosine kinase receptors (6/14; four of those were MET fusions) or DNA repair genes (2/14). Based on the mRNA expression pattern, a cluster of 12 OCCCs characterized by overexpression of tyrosine kinase receptors (TKRs) AKT3, CTNNB1, DDR2, JAK2, KIT, or PDGFRA (p < 0.00001) was identified.ConclusionsThe current work has elucidated the complex genomic and transcriptomic molecular hallmarks of primary OCCCs. Our results confirmed the favorable outcomes of POLEmut and MSI-High OCCC. Moreover, the molecular landscape of OCCC revealed several potential therapeutical targets. Molecular testing can provide the potential for targeted therapy in patients with recurrent or metastatic tumors.
ER  -

STRUZINSKA, Ivana, Nikola HAJKOVA, Jan HOJNY, Eva KRKAVCOVA, Romana MICHALKOVA, Jiri DVORAK, Kristyna NEMEJCOVA, Radoslav MATEJ, Jan LACO, Jana DROZENOVA, Pavel FABIAN, Jitka HAUSNEROVÁ, Gabor MEHES, Petr SKAPA, Marian SVAJDLER, David CIBULA, Filip FRUHAUF, Michaela Kendall KENDALL BARTU and Pavel DUNDR. A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations. \textit{Diagnostic Pathology}. LONDON: BMC, 2023, vol.~18, No~1, p.~1-12. ISSN~1746-1596. Available from: https://dx.doi.org/10.1186/s13000-023-01358-0.

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